This proposal is for a cooperative project to isolate, identify, and study the biological and chemical properties of cardiac stimulants found among certain species of the phylum, Coelenterata, from the Pacific. Crude extracts of nine species of only thirteen tested have shown some degree of a positive inotropic effect on isolated rabbit and rat auricles. One drug, partially purified from Anthopleura xanthogrammica extracts has been studied in some detail. The plan is to isolate the active agents by appropriate techniques; e.g., gel permeation, ion exchange, and adsorption chromatography have been found useful. When physical parameters such as Rf values on TLC or, if protein, gel electrophoresis and electrofocusing are correlated with heart stimulant action, these methods can be used both for separation and for monitoring other separation methods. Separations are monitored by bioassays with isolated rat or rabbit auricles. The purified agents will then be characterized and identified by chemical and spectroscopic techniques including Fourier transform nmr. They will also be subjected to experiments to clarify the mechanism of action on the cardiac muscle and delineate potential practical utility. The primary objectives are to isolate and identify new cardiac stimulants with unique structures, and to study their mode of action. The long range objectives are to provide new structural leads for drugs for heart disease, and, hopefully, new and better drugs for the treatment of heart disease in humans.